Background: People presenting to sexually transmitted infections (STIs) clinics represent an important risk group for HIV infection; prevention strategies will depend on the clinical attendance. Aims: The demographic and clinical changes in clinic attendees in Mumbai, as well as the factors associated with HIV infection in this clinic over a 13-year period, were assessed. Methods: STI clinic data in 3417 individuals (1994 to 2006) were analyzed: clinical presentation, types of STIs, and serology over the 13-year period. We used a logistic regression model to assess socio-demographic and clinical associations with HIV infection. Results: The clinic evaluated 689 patients in 1994 and the number had dropped to 97 in 2006. In 1994, the majority of STIs seen in the clinic were bacterial (53%, 95% confidence interval [CI] 50% to 57%); however, this proportion had dropped in 2006 (28%, 95% CI: 19% to 38%). There was a proportional increase in viral STIs during the same time period. Although women attending the clinic were younger than men, they were more likely to be married. The overall seropositivity for HIV was 28%. Viral STIs were more likely to be associated with HIV than bacterial infections (odds ratio: 1.5, 95% CI: 1.2 to 1.9). Conclusions: Viral infections were the most common STIs in recent years in a tertiary care center in Mumbai. HIV prevalence was high in this population. Thus, these clinical data suggest that STI patients were and continue to be an important group for HIV prevention in the country.